Risk estimation of lifted mask mandates and emerging variants using mathematical model.

Background: More than half of the population in Korea had a prior COVID-19 infection. In 2022, most nonpharmaceutical interventions, except mask-wearing indoors, had been lifted. And in 2023, the indoor mask mandates were eased. Methods: We developed an age-structured compartmental model that distinguishes vaccination history, prior infection, and medical staff from the rest of the population. Contact patterns among hosts were separated based on age and location. We simulated scenarios with the lifting of the mask mandate all at once or sequentially according to the locations. Furthermore, we investigated the impact of a new variant assuming that it has higher transmissibility and risk of breakthrough infection. Results: We found that the peak size of administered severe patients may not exceed 1100 when the mask mandate is lifted everywhere, and 800 if the mask mandate only remains in the hospital. If the mask mandate is lifted in a sequence (except hospital), then the peak size of administered severe patients may not exceed 650. Moreover, if the new variant has both higher transmissibility and immune reduction, the effective reproductive number of the new variant is approximately 3 times higher than that of the current variant, and additional interventions may be needed to keep the administered severe patients from exceeding 2,000, which is the critical level we set. Conclusion: Our findings showed that the lifting of the mask mandate, except in hospitals, would be more manageable if implemented sequentially. Considering a new variant, we found that depending on the population immunity and transmissibility of the variant, wearing masks and other interventions may be necessary for controlling the disease.

Modelling the effects of social distancing, antiviral therapy, and booster shots on mitigating Omicron spread.

As the COVID-19 situation changes because of emerging variants and updated vaccines, an elaborate mathematical model is essential in crafting proactive and effective control strategies. We propose a COVID-19 mathematical model considering variants, booster shots, waning, and antiviral drugs. We quantify the effects of social distancing in the Republic of Korea by estimating the reduction in transmission induced by government policies from February 26, 2021 to February 3, 2022. Simulations show that the next epidemic peak can be estimated by investigating the effects of waning immunity. This research emphasizes that booster vaccination should be administered right before the next epidemic wave, which follows the increasing waned population. Policymakers are recommended to monitor the waning population immunity using mathematical models or other predictive methods. Moreover, our simulations considering a new variant's transmissibility, severity, and vaccine evasion suggest intervention measures that can reduce the severity of COVID-19.

Multi-Faceted Analysis of COVID-19 Epidemic in Korea Considering Omicron Variant: Mathematical Modeling-Based Study.

BACKGROUND: The most recent variant of concern, omicron (B.1.1.529), has caused numerous cases worldwide including the Republic of Korea due to its fast transmission and reduced vaccine effectiveness. METHODS: A mathematical model considering age-structure, vaccine, antiviral drugs, and influx of the omicron variant was developed. We estimated transmission rates among age groups using maximum likelihood estimation for the age-structured model. The impact of non-pharmaceutical interventions (NPIs; in community and border), quantified by a parameter µ in the force of infection, and vaccination were examined through a multi-faceted analysis. A theory-based endemic equilibrium study was performed to find the manageable number of cases according to omicron- and healthcare-related factors. RESULTS: By fitting the model to the available data, the estimated values of µ ranged from 0.31 to 0.73, representing the intensity of NPIs such as social distancing level. If µ < 0.55 and 300,000 booster shots were administered daily from February 3, 2022, the number of severe cases was forecasted to exceed the severe bed capacity. Moreover, the number of daily cases is reduced as the timing of screening measures is delayed. If screening measure was intensified as early as November 24, 2021 and the number of overseas entrant cases was contained to 1 case per 10 days, simulations showed that the daily incidence by February 3, 2022 could have been reduced by 87%. Furthermore, we found that the incidence number in mid-December 2021 exceeded the theory-driven manageable number of daily cases. CONCLUSION: NPIs, vaccination, and antiviral drugs influence the spread of omicron and number of severe cases in the Republic of Korea. Intensive and early screening measures during the emergence of a new variant is key in controlling the epidemic size. Using the endemic equilibrium of the model, a formula for the manageable daily cases depending on the severity rate and average length of hospital stay was derived so that the number of severe cases does not surpass the severe bed capacity.

Seven-Month Analysis of Five SARS-CoV-2 Antibody Assay Results after ChAdOx1 nCoV-19 Vaccination: Significant Decrease in SARS-CoV-2 Antibody Titer.

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0-0.9% at T0, 66.2-92.5% at T1, 98.2-100.0% at T2, and 66.0-100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Risk of COVID-19 transmission in heterogeneous age groups and effective vaccination strategy in Korea: a mathematical modeling study.

OBJECTIVES: This study aims to analyze the possibility and conditions of maintaining an effective reproductive number below 1 using a mathematical model. METHODS: The total population was divided into five age groups (0-17, 18-29, 30-59, 60-74, and ≥75 years). Maximum likelihood estimation (MLE) was used to estimate the transmission rate of each age group. Mathematical model simulation was conducted until December 31, 2021, by establishing various strategies for vaccination and social distancing without considering variants. RESULTS: MLE results revealed that the group aged 0-17 years had a lower risk of transmission than other age groups, and the older age group had relatively high risks of infection. If 70% of the population will be vaccinated by the end of 2021, then simulations showed that even if social distancing was eased, the effective reproductive number would remain below 1 near August if it was not at the level of the third re-spreading period. However, if social distancing was eased and it reached the level of the re-spreading period, the effective reproductive number could be below 1 at the end of 2021. CONCLUSIONS: Considering both stable and worsened situations, simulation results emphasized that sufficient vaccine supply and control of the epidemic by maintaining social distancing to prevent an outbreak at the level of the re-spreading period are necessary to minimize mortality and maintain the effective reproductive number below 1.

Ciclesonide Inhaler Treatment for Mild-to-Moderate COVID-19: A Randomized, Open-Label, Phase 2 Trial.

Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 µg inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group (p = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187-125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group (p = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.